Phase 3 Maternal Safety & Immunogenicity Trial of MVA-BN® in DRC

NCT06844500 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: PIPVac-001 Maternal component
• Study Type: interventional
• Target: 359
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 3 open-label study aims to assess the safety and immune response of the MVA-BN mpox vaccine when administered subcutaneously to pregnant and postpartum women in the Democratic Republic of the Congo (DRC), a population at high risk of mpox infection. The study will be conducted in Boende, Tshuapa Province, DRC. A total of 359 maternal participants, aged 16 to 35 and in their second or third trimester of pregnancy, will be enrolled. Participants will be randomly assigned to receive two subcutaneous doses of the MVA-BN vaccine, given 28 days apart, either during pregnancy (Maternal Group 1) or within 72 hours after delivery (Maternal Group 2). Additionally, pregnant women in any trimester who have been recently exposed to a confirmed mpox case will be enrolled in the post-exposure prophylaxis (PEP) arm (Maternal Group 3), receiving the vaccine as soon as possible after exposure-ideally within four days but up to 14 days if they remain asymptomatic. The study will evaluate the safety, reactogenicity, and immune responses of vaccinated pregnant women compared to healthy adults in the POX-MVA-045 study (NCT06549530) through non-inferiority analyses. Participants will be monitored for immunogenicity and safety for 13 months post-delivery, while neonates will be observed for safety over the same period. The trial will also compare outcomes between women vaccinated during pregnancy and those vaccinated postpartum, assess the transfer of maternal immunity to neonates, and explore correlations between maternal antibody levels in serum and breast milk. This study seeks to provide strong evidence supporting the safety and immunogenicity of the MVA-BN mpox vaccine in pregnancy, contributing to global public health efforts to protect at-risk women and their infants in mpox-endemic regions.

Conditions

Neonate; Maternal Transmission; Mpox; Vaccination; Immunogenicity; Safety; Pregnancy; Postpartum

Keywords

MVA-BN vaccine; mpox; Monkeypox virus; Pregnant women; Newborn; Phase 3; Vaccine; Adults; Randomised; Open-label; Immune transfer; Paediatrics; Obstetrics; Gynaecology; Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic; Neonate; adolescents

Outcome Measures

Primary Outcomes (9)

• Main study: Neutralising antibody response post-dose 2 vaccination with MVA-BN

  To assess the immunogenicity of the MVA-BN standard regimen, administered SC, in eliciting neutralising antibodies against the vaccinia virus in women vaccinated during pregnancy compared to adults of the POX-MVA-045 study at 2 weeks after the second dose.

  14 days after the second dose

• Safety and reactogenicity of the MVA-BN vaccine in pregnant women

  To assess the safety and reactogenicity of the MVA-BN standard regimen, administered SC, in pregnant women compared to adults of the POX-MVA-045 study.

  Throughout the trial period; from first vaccination to 13 months postpartum.

• Neonatal/infant safety outcomes in offspring of vaccinated mothers

  To assess the safety in neonates/infants born to mothers vaccinated during pregnancy and mothers vaccinated postpartum.

  Throughout the trial period; from delivery to 13 months postpartum.

• Maternal, fetal, and neonatal outcomes in vaccinated women

  To describe maternal, foetal and neonatal outcomes in the cohort vaccinated during pregnancy, compared to the cohort vaccinated postpartum (control) and, if possible, the outcomes of pregnancy surveillance in Boende for the duration of the study.

  From vaccination to 13 months postpartum

• Sub-study. Maternal immunity transferred via breastmilk

  To assess immunogenicity in infants at birth by measuring the amount of total binding antibodies against the vaccinia virus, neutralising antibodies against the vaccinia virus, IgG binding antibodies against the vaccinia and mpox viruses in cord blood from women vaccinated during pregnancy compared to women vaccinated in the postpartum.

  At delivery

• Immunogenicity in maternal serum post-vaccination

  To assess the immunogenicity in mothers of the MVA-BN standard regimen, administered SC, in eliciting IgG binding antibodies against vaccinia and monkeypox virus in maternal blood from women vaccinated during pregnancy compared to women vaccinated in the postpartum at baseline (prior to vaccination), 2 weeks after the second dose, at delivery (when not the same as baseline), and at 6 weeks, 12 weeks, 6 months, and 13 months postpartum.

  Baseline to 13 months postpartum

• Maternal immunity transferred via breastmilk (IgA antibodies)

  To assess maternal immunity transferred via breastmilk by measuring IgA binding antibodies against vaccinia and monkeypox virus in breastmilk samples from women vaccinated during pregnancy compared to women vaccinated in the postpartum period in colostrum, at 6 weeks, 12 weeks, 6 months and 13 months postpartum.

  Delivery to 13 months postpartum

• Maternal immunity transferred via breastmilk (IgG antibodies)

  To assess maternal immunity transferred via breastmilk by measuring IgG binding antibodies against vaccinia and monkeypox virus in breastmilk samples from women vaccinated during pregnancy compared to women vaccinated in the postpartum period at 6 weeks and 12 weeks postpartum.

  6 weeks and 12 weeks postpartum

• Persistence of maternal immunity in infants

  To assess persistence of maternal immunity in infants by measuring neutralising antibodies against the vaccinia virus, total binding antibodies against the vaccinia virus, IgG binding antibodies against vaccinia and monkeypox viruses in the infant's blood born from women vaccinated during pregnancy compared to women vaccinated in the postpartum at 6 weeks, 12 weeks, and 6 months postpartum.

  6 weeks to 6 months postpartum

Secondary Outcomes (11)

• Neutralising antibody response in women vaccinated during pregnancy and adult of the POX-MVA-045 study

  Baseline to 13 months postpartum

• Neutralising antibody response in women vaccinated in the immediate postpartum and adult of the POX-MVA-045 study

  Delivery to 13 months postpartum

• Neutralising antibody response in women vaccinated during pregnancy and women vaccinated in the immediate postpartum

  Baseline to 13 months postpartum

• Binding antibody reponse in women vaccinated during pregnancy and adults of the POX-MVA-045 study

  Baseline to 13 months postpartum

• Binding antibody reponse in women vaccinated in the immediate postpartum period and adults of the POX-MVA-045 study

  Throughout the trial period; from first vaccination to 13 months postpartum

Other Outcomes (11)

• Immunogenicity of MVA-BN used as PEP in women exposed during pregnancy

  Baseline to 13 months postpartum

• Binding antibody response in PEP women vaccinated during pregnancy versus non-exposed women

  Delivery to 13 months postpartum

• safety and reactogenicity of the MVA-BN in PEP women vaccinated during pregnancy

  Throughout the trial period; from first vaccination to 13 months postpartum.

Study Arms (4)

Maternal Group 1

ACTIVE COMPARATOR

Women in Maternal Group 1 (vaccination during pregnancy), will receive the first of two MVA-BN vaccine doses, subcutaneously, in the second or third trimester of pregnancy, yet before 32 weeks of gestation. Ideally, both doses are administered during pregnancy.

Biological: MVA-BN standard regimen

Maternal Group 2

ACTIVE COMPARATOR

Women in Maternal Group 2 (vaccinated postpartum), will receive the first of two MVA-BN vaccine doses, subcutaneously, ≤72 hours after delivery, preferably before discharge from the hospital/maternal health clinic (if applicable), unless contraindicated by the gynaecologist.

Biological: MVA-BN standard regimen

Maternal Group 3

ACTIVE COMPARATOR

Women exposed to clinically or laboratory-confirmed mpox cases (Maternal Group 3) will preferably be vaccinated within 4 days after exposure. However the vaccine will be provided until 14 days after exposure if no symptoms are present.

Biological: MVA-BN standard regimen (Administered as PEP)

Historical Arm

OTHER

Historical data from healthy adults aged 18 to 50 years old from the POX-MVA-045 study (NCT06549530), will be used for safety and immunogenicity (non-inferiority) comparisons.

Biological: MVA-BN standard regimen

Interventions

MVA-BN standard regimen BIOLOGICAL

The MVA-BN vaccine, with the active ingredient: Modified Vaccinia Ankara-Bavarian Nordic, will be administered as a standard two-dose regimen at 1x10\^8 TCID50 Inf.U./0.5 mL. The doses will be given 28 days apart (±3 days) via subcutaneous injection into the deltoid muscle, preferably in the non-dominant arm.

Historical Arm; Maternal Group 1; Maternal Group 2

MVA-BN standard regimen (Administered as PEP) BIOLOGICAL

MVA-BN. Post Exposure Prophylaxis (PEP) The MVA-BN vaccine, with the active ingredient: Modified Vaccinia Ankara-Bavarian Nordic, will be administered as a standard two-dose regimen at 1x10\^8 TCID50 Inf.U./0.5 mL. The doses will be given 28 days apart (±3 days) via subcutaneous injection into the deltoid muscle, preferably in the non-dominant arm. For Maternal Group 3, MVA-Bn will be administered as PEP as soon as possible after exposure, preferably within 4 days after exposure. However, as per WHO guidelines, PEP will be offered up to 14 days after exposure if the pregnant woman has not yet developed symptoms.

Maternal Group 3

Eligibility Criteria

• Age: 16 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• The participant must be between 16 and 35 years of age inclusive on the consent day.
• The participant must pass (≥9/10) the Test of Understanding after being advised of the risks and benefits of the trial in a language understood by the participant and before performing any trial-specific procedures.
• Note: For participants 16-17 years old, the parent/legal guardian must also pass the test of understanding.
• Note: If the participant or parent/legal guardian for 16-17-year-olds fails the TOU test on the first attempt, he/she must be retrained on the purpose of the study and must take the test again (2 repeats are allowed). If participants or their parent/legal guardian fail on the third attempt, they should not continue with screening or consenting procedures.
• Note: Maternal Group 3 participants are not restricted to 3 attempts to pass the TOU. For ethical reasons, these participants will be offered unlimited attempts.
• The participant must sign and date an informed consent form (≥18 years old) or assent form (16-17 years old) indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study.
• Note: If the participant is under 18 years of age, informed consent must also be obtained from a parent/legal guardian capable of providing consent. The consent form must be signed and dated by the parent/guardian after they have read and understood the risks and benefits of the trial and before any trial-specific procedures are performed.
• Note: The partner (father of the child) or guardian for the follow-up of the infant after delivery) must also sign an informed consent/assent form (ICF) indicating that they understand the purpose of, and procedures required for, the study and is willing for their child to participate in the study.
• Note: In case the participant, partner, parent/legal guardian cannot read or write, the procedures must be explained in the presence of an impartial (i.e. not involved in the study) third party witness, and informed consent must be obtained from this impartial third party witness.
• The participant must be in her second (13-27 weeks) or early third trimester (28-32 weeks) of pregnancy at the time of vaccination.
• \- Note: Mpox-infected and exposed pregnant women (Maternal group 3) can enrol at any stage of the pregnancy.
• \- Note: Depending on enrolment progress of pregnant women between 13 and 32 weeks gestation, pregnant women in their first trimester may be enrolled but will not be vaccinated until they reach 13 weeks gestation. Sponsor approval needs to be sought to start enrolling pregnant women earlier than 13 weeks gestation.
• The participant and her unborn child must be generally healthy in the investigator's clinical judgment and on the basis of vital signs assessed at day 1 screening with no severe (chronic) conditions (as far as medically known) that might interfere with vaccine assessment.
• \- Note: HIV-positive subjects can be enrolled as long as their general condition is good, i.e., HIV infection under stable Highly Active Antiretroviral Therapy (HAART; no change within the last three month) and/or CD4 count \>500/ μL, no signs or symptoms of immunosuppression. Pregnant HIV-positive participants must agree to attend all prenatal visits foreseen in the time and events schedule for regular follow-up.
• Note: HBV-positive pregnant women will receive treatment according to the National guidelines and can be enrolled as long as their general condition is good. The decision to enrol falls under the discretion of the PI.

You may not qualify if:

• Known history of cowpox, mpox or vaccinia infection.
• Close contact in the 2 weeks before signing the ICF with anyone known to have mpox.
• \- Note: not applicable to Maternal Group 3
• Having received any smallpox or licensed or investigational poxvirus-based (e.g. ACAM2000, MVA-BN based like MVA-BN-Filo) vaccine in the past.
• Must not have received another experimental or non-licensed vaccine within 4 weeks before receiving the MVA-BN vaccine and during the trial.
• Known allergy or history of anaphylaxis or other severe adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines), including known allergy to egg, egg products and aminoglycosides.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g., tris(hydroxymethyl)-amino methane, including a history of allergic asthma.
• Acute or chronic medical condition that, in the opinion of the investigator, would render the trial procedures unsafe or would interfere with the evaluation of responses, including but not limited to neurologic, cardiovascular, respiratory, hepatic, hematologic, rheumatologic, endocrine, gastrointestinal, renal, autoimmune, or immunosuppressive conditions.
• \- Note: Participants with minor acute illnesses such as mild diarrhoea or mild upper respiratory tract infection or temperature ≥38.0ºC at screening will be excluded from enrolment at that time but may be rescheduled for re-screening later if feasible.
• Presence of significant medical conditions or clinically significant findings at screening or vital signs for which, in the opinion of the gynaecologist/medical doctor, participation would not be in the best interest of the participant (e.g., compromise the safety or well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Note: Participants who have recently received treatment for acute, uncomplicated malaria are eligible for participation if at least 3 days have elapsed from the conclusion of a standard, recommended course of therapy for malaria; participants who are acutely ill with malaria at the time of screening should complete therapy and wait an additional 3 days after completion before screening for the study.
• Note: Participants with sickle cell trait can be included.
• History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision at least 6 months prior to screening that is considered to have achieved cure
• Clinically significant mental disorder not adequately controlled by medical treatment.
• Active or recent (within 6 months before screening) chronic alcohol abuse and/or intravenous and/or nasal drug abuse.

Sponsors & Collaborators

• Jean-Pierre Van geertruyden: lead
• PENTA Foundation: collaborator
• Ace Africa: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• Bavarian Nordic: collaborator
• University of Kinshasa: collaborator

Study Sites (1)

Boende Hôpital Général de Référence

Boende, Province de La Tshuapa, Democratic Republic of the Congo

Location

Related Publications (9)

• Lemey G, Lariviere Y, Zola TM, Maketa V, Matangila J, Mitashi P, Vermeiren P, Thys S, De Bie J, Muhindo HM, Ravinetto R, Van Damme P, Van Geertruyden JP. Algorithm for the support of non-related (serious) adverse events in an Ebola vaccine trial in the Democratic Republic of the Congo. BMJ Glob Health. 2021 Jun;6(6):e005726. doi: 10.1136/bmjgh-2021-005726.

  PMID: 34183329 BACKGROUND

• Zola Matuvanga T, Lariviere Y, Lemey G, De Bie J, Milolo S, Meta R, Esanga E, Vermeiren PP, Thys S, Van Geertruyden JP, Van Damme P, Maketa V, Matangila J, Mitashi P, Muhindo-Mavoko H. Setting-up an Ebola vaccine trial in a remote area of the Democratic Republic of the Congo: Challenges, mitigations, and lessons learned. Vaccine. 2022 May 31;40(25):3470-3480. doi: 10.1016/j.vaccine.2022.04.094. Epub 2022 May 9.

  PMID: 35550847 BACKGROUND

• Puri A, Pollard AJ, Schmidt-Mutter C, Laine F, PrayGod G, Kibuuka H, Barry H, Nicolas JF, Lelievre JD, Sirima SB, Kamala B, Manno D, Watson-Jones D, Gaddah A, Keshinro B, Luhn K, Robinson C, Douoguih M; EBL4001 Study Group. Long-Term Clinical Safety of the Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: A Prospective, Multi-Country, Observational Study. Vaccines (Basel). 2024 Feb 17;12(2):210. doi: 10.3390/vaccines12020210.

  PMID: 38400193 BACKGROUND

• Salloum M, Paviotti A, Bastiaens H, Van Geertruyden JP. The inclusion of pregnant women in vaccine clinical trials: An overview of late-stage clinical trials' records between 2018 and 2023. Vaccine. 2023 Nov 22;41(48):7076-7083. doi: 10.1016/j.vaccine.2023.10.057. Epub 2023 Oct 28.

  PMID: 37903681 BACKGROUND

• Lariviere Y, Zola T, Stoppie E, Maketa V, Matangila J, Mitashi P, De Bie J, Muhindo-Mavoko H, Van Geertruyden JP, Van Damme P. Open-label, randomised, clinical trial to evaluate the immunogenicity and safety of a prophylactic vaccination of healthcare providers by administration of a heterologous vaccine regimen against Ebola in the Democratic Republic of the Congo: the study protocol. BMJ Open. 2021 Sep 28;11(9):e046835. doi: 10.1136/bmjopen-2020-046835.

  PMID: 34588237 BACKGROUND

• Schwartz DA, Pittman PR. Mpox (Monkeypox) in Pregnancy: Viral Clade Differences and Their Associations with Varying Obstetrical and Fetal Outcomes. Viruses. 2023 Jul 28;15(8):1649. doi: 10.3390/v15081649.

  PMID: 37631992 BACKGROUND

• Schwartz DA. High Rates of Miscarriage and Stillbirth among Pregnant Women with Clade I Mpox (Monkeypox) Are Confirmed during 2023-2024 DR Congo Outbreak in South Kivu Province. Viruses. 2024 Jul 13;16(7):1123. doi: 10.3390/v16071123.

  PMID: 39066285 BACKGROUND

• Kozlov M. Monkeypox virus: dangerous strain gains ability to spread through sex, new data suggest. Nature. 2024 May;629(8010):13-14. doi: 10.1038/d41586-024-01167-5. No abstract available.

  PMID: 38653833 BACKGROUND

• Bunge EM, Hoet B, Chen L, Lienert F, Weidenthaler H, Baer LR, Steffen R. The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Negl Trop Dis. 2022 Feb 11;16(2):e0010141. doi: 10.1371/journal.pntd.0010141. eCollection 2022 Feb.

  PMID: 35148313 BACKGROUND

Related Links

• MVA-BN
• MVA-BN Product Characteristics

MeSH Terms

Conditions

Mpox, Monkeypox; Smallpox

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Primate Diseases; Animal Diseases; Rodent Diseases

Study Officials

• Jean Pierre Van geertruyden Van geertruyden, Prof. Dr

  Universiteit Antwerpen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr

Model Details: 359 healthy pregnant participants will be randomised (3:2) to receive the standard MVA-BN vaccine of two doses, administered 28 days apart, during pregnancy (N= 215), or in the immediate postpartum (N=144 ).

Study Record Dates

• First Submitted: February 19, 2025
• First Posted: February 25, 2025
• Study Start: June 23, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)